NSAIDs

Question 1

What are the properties of NSAIDs? What are they used to treat?

What’s the difference in the activity of COX-1 and COX-2?

How does Aspirin act on COX?
→ What is useful for?

How do the Older and Newer generation NSAIDs differ?

Answer 1

• Analgesic, Anti-pyretic and Anti-inflammatory drugs used to treat low-grade pain, bone pain, fever and inflammation
• COX-1 is very active, while COX-2 has to be stimulated
• Irreversibly
  → CVD Prophylaxis
• Older drugs inhibit both COX-1 and COX-2, but the Newer drugs inhibit ONLY COX-2

Question 2

MECHANISM OF ACTION:
Analgesic effects:
What substance mainly causes the pain?

Therefore, how are NSAIDs effective here?
→ What type of pain is it useful for?

Anti-pyretic effects:
How does an infection cause a Fever?

Therefore, how are NSAIDs effective here?

Anti-inflammatory effects:
What are the 2 main substances causing the inflammation? How?

How are NSAIDs effective here?

Answer 2

• PGs
• Block PG production = Pain relief
  → Pain associated with inflammatory agents e.g. Arthritis, Headache, Toothache
• Bacterial endotoxins stimulate Macrophages to release IL-1
  o IL-β acts on Hypothalamus to cause PGE2 release
  o ↑PGE2 = Depression of temperature-sensitive neurons = ↑Set-point temperature = Fever
• Block PGE2 production and its effect = No Fever
• PGE2 and PGI2 by Vasodilation and ↑Permeability
• Provide Symptomatic Relief but don’t cure the underlying cause of inflammation

Question 3

EFFECTS:
Cardiovascular:
How does it cause Increased Bleeding?
—————–

Skeletal:
How does it affect the Pain?
—————–

GI:
How do PGs protect the gastric mucosa?

How NSAIDs reduce this protective effect?
→ What does this lead to?
—————–

CNS:
What does NSAID Overdose present with?
→ What can it develop into? When can this happen?
—————–

Genital tract:
What can PGs cause here? So, what can NSAIDs be used for?
—————–

Renal:
How do NSAIDs affect the kidney?

Respiratory:
When shouldn’t NSAIDs be given?

What do toxic doses of Aspirin lead to?

Answer 3

• TXA2 cause platelet aggregation and vasoconstriction, and NSAIDs decrease TXA2
• NSAIDs reduce pain, but don’t treat the underlying cause
• ↑Mucous and ↓Acid secretion
• ↓Mucous and Bicarbonate secretion, ↑Acid and Leukotriene production, ↑Blood loss
  → Ulceration and Bleeding
  —————–
• Paradoxical Hyperpyrexia, Stupor and Coma
  → Reye’s Syndrome when used in children with Influenza or Chicken pox
  —————–
• Pain and smooth muscle spasm during menstruation
  o NSAIDs used for Primary Dysmenorrhoea
  —————–
• ↓Renal blood flow = Renal injury
• ↓Na+ excretion = ↑BV/BP
• Asthma patients
• Initially stimulates respiration, which eventually leads to Hyperventilation = Respiratory Alkalosis

Question 4

What else can NSAIDs be used for?

Answer 4

• Closure of Patent Ductus Arteriosus
• ↓Colonic polyps and prevents Colon cancer
• ↓Risk of Alzheimer’s
• Post-operative pain relief
• Renal colic pain relief

Question 5

Ulcerative Colitis:
What is it? What’s it due to?

What is the First-line of treatment?
→ How does it work?
→ What are its side effects?

Gout:
What is it? What’s it due to?

What drugs can be given?
→ How does Naproxen work?
→ What are its side effects?

Answer 5

• Inflammation of Bowel lining due to ↑PGs
• Aminosalicylates e.g. Sulfasalazine
  → Inhibits COX and LOX
  → Indigestion, Nausea, Diarrhoea, Abdominal pain, Dizziness, Insomnia, Tinnitus, Coughing, Rash
• Accumulation of Uric acid crystals in joints causing inflammation and pain - Due to Hyperuricaemia (↑Uric acid)
• Naproxen, Indomethacin
  → Inhibits COX1/2
  → Indigestion, Nausea, Dizziness, Blurred vision, Diarrhoea, Abnormal LFTs, Water retention, Tinnitus, Rash